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Drug discovery was initially attributed to coincidence or experimental research. Historically, the traditional approaches were complex, lengthy, and expensive, entailing costly random screening of synthesized compounds or natural products coupled with in vivo validation largely depending on the availability of appropriate animal models. Currently, in silico modeling has become a vital tool for drug discovery and repurposing. Molecular docking and dynamic simulations are being used to find the best match between a ligand and a molecule, an approach that could help predict the biomolecular interactions between the drug and the target host. Beauvericin (BEA) is an emerging mycotoxin produced by the entomopathogenic fungus Beauveria bassiana, being originally studied for its potential use as a pesticide. BEA is now considered a molecule of interest for its possible use in diverse biotechnological applications in the pharmaceutical industry and medicine. In this manuscript, we provide an overview of the repurposing of BEA as a potential therapeutic agent for multiple diseases. Furthermore, considerable emphasis is given to the fundamental role of in silico techniques to (i) further investigate the activity spectrum of BEA, a secondary metabolite, and (ii) elucidate its mode of action. [ABSTRACT FROM AUTHOR]

Chlorpyrifos poses a danger to the environment as a result of its toxicity and endurance in soil and water. Bioremediation of pesticide-polluted soils is one of the most promising approaches for removing contaminants from the environment. This study aimed to isolate and identify chlorpyrifos-degrading bacterial strains and test their biodegradation capabilities and their roles in plant growth. The 16S rDNA gene sequencing identified the two efficient chlorpyrifos-degrading bacterial strains as Stenotrophomonas maltophilia (RS1) and Acinetobacter calcoaceticus (RS3), which significantly (p < 0.01) degraded 71.3% and 73.5% of chlorpyrifos in the liquid medium, respectively, compared to 80% degradation (p < 0.01) when cultured as a consortium within 48 h. The bioremediation of artificially chlorpyrifos-contaminated soils varied between 84.4% and 90.11% (p < 0.01), depending on the used bacterium and soil sterilization status. Furthermore, the enzymes embroiled in the degradation mechanism were sprinkled all over the cells but with different portions. Experiments on plant growth revealed that chlorpyrifos hurt lettuce growth. The presence of RS1 and RS3, on the other hand, demonstrated considerable lettuce growth-enhancing traits in terms of germination percentages, shoot and root lengths and weights. Our isolates could be promising candidates in the bioremediation of chlorpyrifos-contaminated sites in conjunction with their contribution as biofertilizers. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a neglected tropical disease infecting the world's poorest populations. Miltefosine (ML) remains the primary oral drug against the cutaneous form of leishmaniasis. The ATP-binding cassette (ABC) transporters are key players in the xenobiotic efflux, and their inhibition could enhance the therapeutic index. In this study, the ability of beauvericin (BEA) to overcome ABC transporter-mediated resistance of Leishmania tropica to ML was assessed. In addition, the transcription profile of genes involved in resistance acquisition to ML was inspected. Finally, we explored the efflux mechanism of the drug and inhibitor. The efficacy of ML against all developmental stages of L. tropica in the presence or absence of BEA was evaluated using an absolute quantification assay. The expression of resistance genes was evaluated, comparing susceptible and resistant strains. Finally, the mechanisms governing the interaction between the ABC transporter and its ligands were elucidated using molecular docking and dynamic simulation. Relative quantification showed that the expression of the ABCG sub-family is mostly modulated by ML. In this study, we used BEA to impede resistance of Leishmania tropica . The IC 50 values, following BEA treatment, were significantly reduced from 30.83, 48.17, and 16.83 µM using ML to 8.14, 11.1, and 7.18 µM when using a combinatorial treatment (ML + BEA) against promastigotes, axenic amastigotes, and intracellular amastigotes, respectively. We also demonstrated a favorable BEA-binding enthalpy to L. tropica ABC transporter compared to ML. Our study revealed that BEA partially reverses the resistance development of L. tropica to ML by blocking the alternate ATP hydrolysis cycle., Competing Interests: The authors declare no conflict of interest.